Method of preparing neural tissue of the brain for subsequent electrical stimulation

ABSTRACT

Methods are disclosed of preparing neural tissue of the brain for subsequent electrical stimulation. For example, first, second and third electrodes may be placed in close proximity to tissue of a patient&#39;s brain. A hyperpolarizing electrical pre-pulse may be applied to the tissue through the first electrode wherein the tissue is more susceptible to subsequent electric stimulation, or a depolarizing electrical pre-pulse may be applied to the tissue through the first electrode wherein the tissue is less susceptible to subsequent electric stimulation. Other exemplary embodiments are also disclosed.

RELATED APPLICATION

This application is a divisional of prior application Ser. No.10/140,387, filed May 7, 2002, which in turn is a continuation ofapplication Ser. No. 09/591,957, filed Jun. 12, 2000, now abandoned,which is a divisional of application Ser. No. 09/070,264, filed Apr. 30,1998, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to an apparatus and method for electricallystimulating neural tissue including, but not limited to, a spinal cord.More specifically, this invention relates to an apparatus and method forapplying a precursor electrical pulse to neural tissue prior to astimulation pulse with the first pulse “conditioning” the tissue for theapplication of the stimulation pulse.

2. Description of the Prior Art

Nerve cells in the brain and the spinal cord have a variety of shapesand sizes. A typical nerve cell has the shape shown in FIG. 1 generallylabeled 1. The classical parts of nerve cell 1 are the cell body 2, thedendritic tree 3 and the axon 4 (including its terminal branches). Nervecells convey information to other cells at junctions called synapses.

An important property of the nerve cell is the electrical potential thatexists across the cell's outer membrane 5. Normally, when cell 1 is atrest, the inside 6 of cell 1 is 70-80 mV negative with respect to theoutside 7 of cell 1. As shown in FIG. 2, cell 1 has chemical pumps 8imbedded in the cell membrane 5. Pumps 8 consume energy to move sodiumions 9 outside and potassium ions 10 into the cell 1 to maintain theconcentration gradients and therefore the electrical potentialdifference across membrane 5.

The membrane 5 of the axon 4 has specific dynamic properties related toits function to transmit information. In man, like in other mammals, itcontains sodium channels 11 and leakage channels 12. Membrane 5 has avoltage and time dependent sodium conductivity that is related to thenumber of open sodium channels. Channels 11 open and close in responseto changes in the potential across the membrane 5 of the cell 1. Whenthe membrane 5 is in its resting state (70-80 mV negative at theinside), only few sodium channels 11 are open. However, when theelectrical potential across membrane 5 is reduced (membranedepolarization) to a value called the excitation threshold, the sodiumchannels 11 open up allowing sodium ions 9 to rush in (excitation). As aresult, the electrical potential across membrane 5 changes by almost 100mV, so that the inside 6 of the axon 4 gets positive with respect to theoutside 7.

After a short time the sodium channels 11 close again and the restingvalue of the membrane potential is restored by the flow of ions throughthe leakage channels 12. This transient double reversal of the potentialacross the membrane 5 is named “action potential”. The action potential,which is initiated at a restricted part of membrane 5, also depolarizesadjacent portions of the membrane 5 up to their excitation threshold.Channels 11 in these portions begin to open, resulting in an actionpotential at that portion of the membrane 5 which then affects the nextsection of membrane 5 and so on and so on. In this way the actionpotential is propagated as a wave of electrical depolarization along thelength of the axon 4 (FIG. 3).

After an action potential has been generated, there is a refractoryperiod during which nerve cell 1 cannot generate another actionpotential. The sodium channels 11 do not open again when the membrane 5is depolarized shortly after its excitation. The effect of therefractory period is that action potentials are discrete signals. Trainsof propagating action potentials transmit information within the nervoussystem, e.g. from sense organs in the skin to the spinal cord and thebrain.

There are two categories of nerve fibers that carry sensory informationfrom remote sites to the spinal cord, small diameter afferent nervefibers 13 and large diameter afferent nerve fibers 14. Generallyspeaking, the small diameter afferent nerve fibers 13 carry pain andtemperature information to the spinal cord while the large diameterafferent nerve fibers 14 carry other sensory information such asinformation about touch, skin pressure, joint position and vibration tothe spinal cord. As shown in FIG. 4, both the small and large diameterafferent nerve fibers 13, 14 enter the spinal cord 16 at the dorsalroots 17. Only large diameter nerve fibers 14 contribute branches to thedorsal columns 15.

Melzack and Wall published a theory of pain which they called the “gatecontrol theory.” (R. Melzack, P. D. Wall, Pain Mechanisms: A new theory.Science 1965, 150:971-979) They reviewed past theories and data on painand stated that there seems to be a method to block pain at the spinallevel. Within the dorsal horn of gray matter of the spinal cord, thereis an interaction of small and large diameter afferent nerve fibers 13,14 through a proposed interneuron. When action potentials aretransmitted in the large diameter afferent nerve fibers 14, actionpotentials arriving along small diameter nerve fibers 13 (paininformation) are blocked and pain signals are not sent to the brain.Therefore, it is possible to stop pain signals of some origins byinitiating action potentials in the large diameter fibers. The type ofpain that can be blocked by such activity is called neuropathic pain.Chronic neuropathic pain often results from damage done to neurons inthe past.

Spinal Cord Stimulation (SCS) is one method to preferentially induceaction potentials in large diameter afferent nerve fibers 14. Thesefibers 14 bifurcate at their entry in the dorsal columns 15 into anascending and a descending branch (dorsal column fiber), each havingmany ramifications into the spinal gray matter to affect motor reflexes,pain message transmission or other functions. Only 20% of the ascendingbranches reach the brain (for conscious sensations).

Action potentials in the large diameter nerve fibers 14 are usuallygenerated at lower stimulation voltages than action potentials in smalldiameter nerve fibers 13. While the dorsal roots 17 could be stimulatedto cause action potentials in the large diameter afferent nerve fibers14, stimulation there can easily cause motor effects like muscle crampsor even uncomfortable sensations. A preferred method is to placeelectrodes near the midline of spinal cord 16 to limit stimulation ofthe nerve fibers in dorsal root 17.

Today, SCS systems use cylindrical leads or paddle-type leads to placemultiple electrodes in the epidural space over the dorsal columns 15.Often the surgeon will spend an hour or more to position the leadsexactly, both to maximize pain relief and to minimize side effects. Oneof the current problems with SCS is the preferential stimulation ofnerve fibers in the dorsal roots (dorsal root nerve fibers) instead ofnerve fibers in the dorsal columns (dorsal column fibers) especially atmid-thoracic and low-thoracic vertebral levels. This is in part becausethe largest dorsal root fibers 14 have larger diameters than the largestnearby dorsal column fibers. Other factors contributing to the smallerstimulus needed to excite dorsal root fibers are the curved shape of thedorsal root fibers and the stepwise change in electrical conductivity ofthe surrounding medium at the entrance of a dorsal root into the spinalcord (J. J. Struijk et al., IEEE Trans Biomed Eng 1993, 40:632-639).Stimulation of fibers in one or more dorsal roots results in arestricted area of paresthesia. That is, paresthesia is felt in only afew dermatomes (body zones innervated by a given nerve). In contrast,dorsal column stimulation results in paresthesia in a large number ofdermatomes.

One approach to suppress the activation of dorsal root fibers andthereby favor dorsal column stimulation has been the application of anelectric field to the tissue where the shape of the electric field ischangeable and, as a result, where the location of the electric field inthe tissue is steerable. This technique has been described in U.S. Pat.No. 5,501,703 entitled Multichannel Apparatus For Epidural Spinal CordStimulation that issued Mar. 26, 1996 with Jan Holsheimer and JohannesJ. Struijk as inventors. As described in this patent, the electric fieldproduced by electrodes described in the patent is shaped and steered topreferentially activate dorsal column fibers instead of dorsal rootfibers. The invention is based on the principle that nerve fibers aredepolarized (and eventually excited) when a nearby electrode is at anegative potential, while the opposite (hyperpolarization) occurs nearelectrodes at a positive potential. A negative electrode is named acathode, because it attracts ions with a positive charge (cations). Apositive electrode is named an anode, because it attracts negative ions(anions).

In practice, electrodes are typically placed epidurally. It appears thatwhere the distance between the epidurally located electrodes and thespinal cord is large, such as at the mid-thoracic and low-thoraciclevels, the method described in the '703 patent may still notsufficiently favor stimulation of the dorsal column fibers over dorsalroot fibers in a number of patients (J. Holsheimer et al., Amer JNeuroradiol 1994, 15:951-959). The relatively large dorsal root fibersmay still generate action potentials at lower voltages than will nearbydorsal column fibers. As a result, the dorsal column fibers that aredesired to be stimulated have a lower probability to be stimulated thanthe dorsal root fibers, which are not desired to be stimulated and whichproduce the undesirable side effects noted above. Therefore, a differentor concurrent approach may be needed.

Grill and Mortimer (IEEE Eng Med Biol Mag 1995, 14:375-385) have shownthat applying an appropriate pre-pulse, sub-threshold to the productionof an action potential, to neural tissue can make the nerve fiberseither more or less excitable. More particularly, when an appropriatesub-threshold depolarizing (cathodic) pre-pulse (DPP) is applied toneural tissue in advance of a cathodic stimulation pulse, the nervemembrane 5 will be slightly depolarized, causing a reduction of the(small) number of open sodium channels 11 (FIG. 2). As a result, theexcitation threshold of the axon 4 will increase and a stronger stimulusis needed to evoke an action potential than without a DPP. Conversely,when an appropriate hyperpolarizing (anodic) pre-pulse (HPP) is appliedto neural tissue in advance of a cathodic stimulation pulse, the nervemembrane 5 will be hyperpolarized, causing an increase of the number ofopen sodium channels 11. As a result, the excitation threshold of theaxon 4 will decrease and a weaker stimulus is needed to initiate anaction potential than without an HPP.

The teaching of Grill and Mortimer is incorporated herein in itsentirety. HPP make nerve fibers more excitable while DPP make nervefibers less excitable. Grill and Mortimer have shown that for a 100 μscathodic pulse without HPP or DPP and having a sub-threshold amplitude,the application of an (anodic) HPP pulse prior to the previouslysub-threshold cathodic pulse can enable the identical 100 μs pulse tonow trigger an action potential. In particular, if a 400 μs HPP of 90%of the threshold amplitude for a 500 μs pulse, but opposite in sign,precedes the 100 μs pulse of sub-threshold amplitude, the 100 μs pulsewill create an action potential in the nerve fiber.

Conversely, Grill and Mortimer have shown that for a 100 μs cathodicpulse without HPP or DPP and having a sufficient amplitude(supra-threshold) to trigger an action potential, the application of a(cathodic) DPP pulse prior to the previously supra-threshold cathodicpulse can cause the identical 100 μs pulse to now be sub-threshold. Inparticular, if a 400 μs DPP of 90% of threshold amplitude for a 500 μspulse and of the same sign precedes the 100 μs pulse of thresholdamplitude, the 100 μs pulse will now be sub-threshold and will notcreate an action potential in the nerve fiber.

Deurloo et al. (Proc. 2^(nd) Ann Conf Int Funct Electrostim Soc, 1997,Vancouver, pp. 237-238) have recently shown that the effect of DPP canbe obtained more efficiently when using an exponentially increasingcathodic current instead of a rectangular current shape.

SUMMARY OF THE INVENTION

A system and method is described for preferentially stimulating dorsalcolumn fibers while avoiding stimulation of dorsal root fibers. Theinvention applies hyperpolarizing (anodic) pre-pulses (HPP) anddepolarizing (cathodic) pre-pulses (DPP) to neural tissue, such asspinal cord tissue, through a lead placed over the spinal cord havingthe electrodes arranged on a line approximately transverse to the axisof the spine. To increase the threshold needed to stimulate dorsal rootfibers, the anodal pulse given by each lateral contact of the electrode,is preceded by a DPP. The cathodic pulse, given simultaneously by thecentral electrode contact is preceded by an HPP, thereby reducing thestimulation threshold for the dorsal column fibers.

It is therefore a primary object of the invention to provide a systemand method for treating pain by spinal cord stimulation (SCS) bypreferentially stimulating dorsal column fibers over dorsal root fibers.

It is another primary object of the invention to provide a system andmethod for electrically stimulating the spinal cord by preferentiallystimulating dorsal column fibers over dorsal root fibers.

It is another primary object of the invention to provide a system andmethod for electrically and preferentially stimulating selected regionsof the brain and peripheral nerves.

It is another object of the invention to provide a system and method fortreating pain by SCS by preferentially stimulating dorsal column fibersover dorsal root fibers that is easy to use.

It is another object of the invention to provide a system and method forelectrically stimulating the spinal cord by preferentially stimulatingdorsal column fibers over dorsal root fibers that is easy to use.

These and other objects of the invention will be clear to those skilledin the art from the description contained herein and more particularlywith reference to the Drawings and the Detailed Description of theInvention where like elements, wherever referenced, are referred to bylike reference numbers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of a nerve cell.

FIG. 2 is a schematic view of the chemical pumps and voltage dependentchannels in the membrane of the nerve cell of FIG. 1.

FIG. 3 is a schematic view of the nerve cell of FIG. 1 showing thepropagation of an action potential.

FIG. 4 is a cross-sectional view of the spine.

FIG. 5 is a schematic view of the present invention.

FIG. 6 is a graphic representation of the signals applied to theelectrodes of the preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

A system of the present invention is shown in FIG. 5 generally labeled10. System 10 includes an electric signal generator that is preferablyan implantable electric pulse generator (IPG) 12. IPG 12 preferably is adevice having at least two channels that may be independentlycontrollable in amplitude, frequency, timing and pulse width. In thepreferred embodiment, IPG 12 has two such channels.

The pulse generator may also be a pulse generator that is connected toan implanted receiver that receives power and programming from anexternal transmitter by RF coupling. Such a system could be a Matrix®radio-frequency pulse generator available from Medtronic, Inc. ofMinneapolis, Minn.

Alternately, an IPG 12 with three independently controllable channelscan be used. In another alternate embodiment, IPG 12 may have a singlechannel. Such a system could be an Itrel® implantable pulse generatoravailable from Medtronic, Inc. of Minneapolis, Minn. It is also to beunderstood that IPG 12 may be any device providing electrical signalswhether or not those signals are electrical pulses. For example, IPG 12may, instead of providing electrical pulses, provide electrical signalsof varying amplitude and frequency such as sinusoidal waves or otherrelatively continuous signals.

IPG 12 is electrically connected to a lead 14 for applying stimulationpulses. Lead 14 has a series of electrodes 16 a,b,c arranged on a line20 on a paddle 18. In the preferred embodiment, electrodes 16 arelocated along line 20 so that when lead 14 is implanted in a patientalong a patient's spinal cord, line 20 is transverse to the axis of thespinal cord. In an alternate embodiment, electrodes 16 a,b,c are locatedalong a line 20′ that is parallel to the axis of the spinal cord. Ineither embodiment, electrode 16 b is located between electrodes 16 a and16 c.

In the embodiment where IPG 12 has one channel, electrodes 16 a,c areattached to one output of IPG 12, while electrode 16 b is connected tothe other output. In the embodiment where IPG 12 has two or morechannels, electrode 16 b is attached to the output the channels have incommon, while each electrode 16 a,c is attached to the non-common outputof a different channel.

In operation, lead 14 is implanted epidurally by techniques well knownto those in the art and advanced to a desired location along thepatient's spinal column. In this position, with the preferred embodimentof lead 14, line 20 containing electrodes 16 a,b and c is locatedtransverse to the axis of the spinal cord.

With lead 14 in place and connected to IPG 12, a pulse pattern accordingto the present invention is applied to electrodes 16 as will bedescribed hereafter. This pulse pattern will produce the desiredobjective of preferentially stimulating the dorsal column fibers whileinhibiting the stimulation of the dorsal root fibers.

The pulse pattern presented to electrodes 16 is shown in FIG. 6. Thepulse pattern presented to electrodes 16 a,c is labeled “A”. Thesimultaneous pulse pattern of opposite sign presented to electrode 16 bis labeled “B”.

Pulse pattern “A” has two parts, a depolarizing (cathodic) pre-pulse(DPP) labeled A1 followed by an anodic pulse A2. The DPP A1 shoulddesensitize membranes of the neural tissue to be affected by thestimulation pulse A2. Experience has shown that an effective DPP A1 isabout 500 μs long and has an amplitude of about 90% of the thresholdamplitude for a 500 μs pulse. The DPP A1 should be opposite in sign tothe stimulation pulse A2 as will be described hereafter. Although aspecific DPP A1 has been described, any DPP shape that results indesensitization of the membranes of neural tissue being stimulated maybe used and is within the scope of the invention.

Immediately after the pre-pulse A1, an anodic stimulation pulse A2 isapplied. Stimulation pulse A2 has sufficient amplitude and duration togreatly inhibit the production of action potentials in neural tissuenear electrodes 16 a,c. The operation of such a stimulation pulsethrough the configuration of lead 14 may preferably apply a conceptknown as “transverse tripolar stimulation” that is explained in detailin U.S. Pat. No. 5,501,703 issued to Jan Holsheimer and Johannes J.Struijk on Mar. 26, 1996 entitled “Multichannel Apparatus for EpiduralSpinal Cord Stimulator”, the teachings of which are incorporated byreference in its entirety.

Pulse pattern “B” also has two parts, an anodic hyperpolarizingpre-pulse (HPP) B1 followed by a cathodic pulse B2. The HPP B1 shouldsensitize the cell membranes of the neural tissue to be affected by thestimulation pulse B2. Because all current flows between electrode 16 band electrodes 16 a,c, the current of pulse B1 is identical to the sumof the currents of pulses A1 at electrodes 16 a and 16 c andsimultaneous. Likewise, the current of pulse B2 is identical to the sumof the currents of A2 at electrodes 16 a and 16 c and simultaneous. Inaddition, pulses A1 and A2 should be opposite in sign to pulses B1 andB2, respectively. Because DPP A1 is about 500 μs long, HPP B1 is alsoabout 500 μs long. Although a specific HPP B1 has been described, anyHPP shape that results in sensitization of the membranes of neuraltissue being stimulated may be used and is within the scope of theinvention. Immediately after the HPP B1, a cathodic pulse B2 is applied.Pulse B2 has sufficient amplitude and duration to generate actionpotentials in neural tissue near electrode 16 b.

To avoid “anodal break excitation”, the duration and the magnitude ofthe hyperpolarizing pulse A2 might have to be limited to avoidactivation of nerve cells at the end of this pulse. Alternately, thetrailing edge of the pulse might need to be ramped down (c.f., Z. P.Fang and J. T. Mortimer, IEEE Trans Biomed Eng 1991, 38:168-174; G. S.Brindley, M. D. Craggs, J Neurol Neurosurg Psychiatry 1980,43:1083-1090).

In the preferred embodiment electrode 16 b is placed generally over thecenter of the spinal cord, and consequently near the dorsal columns 15,but away from the left and right dorsal roots 17. The HPP B1 will causethe dorsal column fibers closest to electrode 16 b to be hyperpolarizedand therefore more susceptible to the subsequent stimulation pulse B2.Conversely, electrodes 16 a and 16 c are located near the nerve fibersin the dorsal roots 17. The DPP A1 will cause the nerve fibers in thedorsal roots 17 to be slightly depolarized and therefore less likely torespond to the stimulation pulse A2. As a result, stimulation of dorsalroot fibers can be avoided at a higher amplitude of the stimulationpulse A2 with a DPP A1 than it could be without a DPP A1.

As can be seen in FIG. 6, in the embodiment of IPG 12 with a singlechannel, pre-pulses A1 and B1 are equal in time as are anodic pulse A2and cathodic pulse B2. In the embodiment having separate channels of IPG12 connected to 16 a-b and 16 b-c, stimulation pulses A2 and B2 may havedifferent amplitudes for contacts 16 a-b and 16 b-c. However, thesepulses should largely overlap in time to create an electrical fieldpromoting the stimulation of dorsal column fibers and the inhibition ofdorsal root fibers, according to the concept known as “transversetripolar stimulation” and described in U.S. Pat. No. 5,501,703 and in apaper (Med Biol Eng Comp 1996, 34:273-279). Likewise, pre-pulses A1 andB1 should largely overlap in time to promote the sensitization of dorsalcolumn fibers and desensitization of dorsal root fibers. When a thirdchannel of IPG 12 is available, this channel can be connected to acontact 16 a,b,c and to the metal casing of the IPG. For either case,for every stimulation pulse the invention anticipates the application ofpre-pulses.

It is believed to be important to have a zero net charge to and fromelectrodes 16 a,b,c for each stimulation pulse. This minimizes electrodedegradation and cell trauma. Ordinarily, a zero net charge isaccomplished by applying a charge-balancing pulse to an electrode,opposite in sign and immediately after a stimulation pulse applied tothe same electrode. The charge-balancing pulse has an amplitude andduration compensating for the charge injected by the stimulation pulse.This is usually accomplished by a charge-balancing pulse having a longduration and a low amplitude.

The application of cathodic and anodic pre-pulses A1 and B1 makes iteasier to achieve this zero net charge, because these pre-pulses areopposite in sign to pulses A2 and B2, respectively. Therefore, theapplication of a pre-pulse makes the charge-balancing pulse smaller. Ifpre-pulses A1 and B1 are chosen correctly, the charge-balancing pulsesmay be eliminated altogether.

The application of HPP and DPP has been described in connection withstimulation of neural tissue in the spinal cord. The principal of theinvention can be applied to neural tissue generally where it is desiredto shield certain cells from the effects of nearby cathodal stimulation.For example, it may be desirable to preferentially stimulate certainbrain cells while avoiding stimulating other nearby brain cells.

In one embodiment, a lead 14 having a first electrode 16 a and a secondelectrode 16 b would be inserted in the brain and moved to the desiredlocation with electrode 16 b near the area to be preferentiallystimulated and electrode 16 a moved near an area that it is desirablenot to stimulate or to inhibit. A hyperpolarizing pre-pulse B1 may beapplied to electrode 16 b and a depolarizing pre-pulse A1 applied toelectrode 16 a. These pulses may both be applied or may be applied inthe alternative, that is, either a hyperpolarizing pre-pulse B1 or adepolarizing pre-pulse A1 may be applied to electrode 16 b.

In a variant of this embodiment, a lead 14 having two outside electrodes16 a,c and a center electrode 16 b would be inserted in the brain andmoved to the desired location with electrode 16 b near the area to bepreferentially stimulated and electrodes 16 a,c moved near the areasthat it is desirable not to stimulate or to inhibit. A hyperpolarizingpre-pulse B1 may be applied to electrode 16 b and a depolarizingpre-pulse A1 applied to electrodes 16 a,c. These pulses may both beapplied or may be applied in the alternative.

In a variant of this embodiment, as before, a lead 14 having two outsideelectrodes 16 a,c and a center electrode 16 b would be inserted in thebrain and moved to the desired location. In this variant, electrode 16 bis placed near the area to be preferentially inhibited while electrodes16 a,c are moved near the areas that it is desirable to stimulate. Adepolarizing pre-pulse A1 is sent to electrode 16 b while ahyperpolarizing pre-pulse B1 is sent to electrodes 16 a,c.

In another embodiment, a lead 14 having two outside electrodes 16 a,cand a center electrode 16 b would be placed on or near the surface ofthe brain, for example, on the cortex, and moved to the desired locationwith electrode 16 b near the area to be preferentially stimulated andelectrodes 16 a,c moved near the areas that it is desirable not tostimulate or to inhibit. The lead is then operated as described above inconnection with stimulating spinal cord tissue. In this embodiment, thelead may be placed either sub-durally or epidurally.

In any of the embodiments of the lead having three electrodes, whetherfor use on the spine, in the brain or on peripheral nerve, theelectrodes may be arranged along a single line or may be arranged in atwo or three-dimensional array, that is, so that only two electrodes areon a single line.

Likewise, it may be desirable to preferentially stimulate certain nervefibers in a peripheral nerve or spinal nerve root while avoidingstimulating other nearby nerve fibers. In one embodiment, a lead 14having two outside electrodes 16 a,c and a center electrode 16 b wouldbe placed around part of a nerve bundle so that line 20 is transverse tothe axis of the nerve bundle and electrode 16 b is near the nerve fibersto be preferentially stimulated. The lead is then operated as describedabove in connection with stimulating spinal cord tissue.

In another embodiment, a number of electrodes are placed at the insideof a nerve cuff, transverse to the axis of the nerve bundle. Oneelectrode near the nerve fibers to be preferentially stimulated isselected as the electrode 16 b, while the neighboring ones are selectedas electrodes 16 a,c. The lead is then operated as described above inconnection with stimulating spinal cord tissue.

While this invention has been described with reference to illustrativeembodiments, this description is not intended to be constructed in alimiting sense. Various modifications of the illustrative embodiments,as well as other embodiments of the invention, will be apparent topersons skilled in the art upon reference to this description. It istherefore contemplated that the appended claims will cover any suchmodifications or embodiments as fall within the true scope of theinvention.

1. A method of preparing neural tissue of the brain for subsequentelectrical stimulation comprising the steps of: placing first, secondand third electrodes in close proximity to tissue of a patient's brain;applying a hyperpolarizing electrical pre-pulse to the tissue throughthe first electrode wherein the tissue is more susceptible to subsequentelectric stimulation; applying a depolarizing electrical pre-pulse tothe tissue through a second electrode wherein the tissue near the secondelectrode is less susceptible to subsequent electric stimulation; andapplying depolarizing electrical pre-pulse to the tissue through a thirdelectrode wherein the tissue near the third electrode is lesssusceptible to subsequent electric stimulation.
 2. The method of claim 1wherein the step of placing first, second and third electrodes in closeproximity to tissue of a patient's brain includes placing the firstelectrode in tissue of a patient's brain.
 3. The method of claim 2wherein the step of placing first, second and third electrodes in closeproximity to tissue of a patient's brain includes placing the secondelectrode in tissue of a patient's brain.
 4. The method of claim 3wherein the step of placing first, second and third electrodes in closeproximity to tissue of a patient's brain includes placing the thirdelectrode in tissue of a patient's brain.
 5. The method claim 4 furthercomprising the steps of: implanting a source of electrical pulses withinthe patient's body; and electrically connecting the source of electricalpulses to the first, second and third electrodes.
 6. The method of claim3 further comprising the steps of: implanting a source of electricalpulses within the patient's body; and electrically connecting the sourceof electrical pulses to the first, second and third electrodes.
 7. Themethod of claim 2 further comprising the steps of: implanting a sourceof electrical pulses within the patient's body; and electricallyconnecting the source of electrical pulses to the first, second andthird electrodes.
 8. The method of claim 1 wherein the step of placingfirst, second and third electrodes in close proximity to tissue of apatient's brain includes placing the first electrode on the surface of apatient's brain.
 9. The method of claim 8 wherein the step of placingfirst, second and third electrodes in close proximity to tissue of apatient's brain includes placing the second electrode on the surface ofa patient's brain.
 10. The method of claim 9 wherein the step of placingfirst, second and third electrodes in close proximity to tissue of apatient's brain includes placing the third electrode on the surface of apatient's brain.
 11. The method of claim 10 further comprising the stepsof: implanting a source of electrical pulses within the patient's body;and electrically connecting the source of electrical pulses to thefirst, second and third electrodes.
 12. The method of claim 9 furthercomprising the steps of: implanting a source of electrical pulses withinthe patient's body; and electrically connecting the source of electricalpulses to the first, second and third electrodes.
 13. The method ofclaim 8 further comprising the steps of: implanting a source ofelectrical pulses within the patient's body; and electrically connectingthe source of electrical pulses to the first second and thirdelectrodes.
 14. The method of claim 1 wherein the step of placing first,second and third electrodes in close proximity to tissue of a patient'sbrain includes placing the first electrode near the surface of apatient's brain.
 15. The method of claim 14 wherein the step of placingfirst, second and third electrodes in close proximity to tissue of apatient's brain includes placing the second electrode near the surfaceof a patient's brain.
 16. The method of claim 15 wherein the step ofplacing first, second and third electrodes in close proximity to tissueof a patient's brain includes placing the third electrode near thesurface of a patient's brain.
 17. The method of claim 16 furthercomprising the steps of: implanting a source of electrical pulses withinthe patient's body; and electrically connecting the source of electricalpulses to the first, second and third electrodes.
 18. The method ofclaim 15 further comprising the stops of: implanting a source ofelectrical pulses within the patient's body; and electrically connectingthe source of electrical pulses to the first, second and thirdelectrodes.
 19. The method of claim 14 further comprising the steps of:implanting a source of electrical pulses within the patient's body; andelectrically connecting the source of electrical pulses to the first,second and third electrodes.
 20. A method of preparing neural tissue ofthe brain for subsequent electrical stimulation comprising the steps of:providing a source of electrical pulses; providing a first electrode;providing an electrical return path; connecting the first electrode tothe source of electrical pulses; placing the first electrode in tissueof a patient's brain; applying a hyperpolarizing electrical pre-pulse tothe tissue through the first electrode wherein the tissue is moresusceptible to subsequent electric stimulation; and applying asubsequent depolarizing electrical pulse to the tissue through the firstelectrode.
 21. The method of claim 20, wherein the step of providing anelectrical return path includes the step of providing an electricalreturn path that includes a second electrode.
 22. The method of claim 20wherein the step of providing an electrical return path includes thestep of providing an electrical return path that includes the source ofelectrical pulses.
 23. The method of claim 20 wherein the step ofproviding a first electrode includes the step of providing a secondelectrode spaced from the first electrode and further comprising thestep of connecting the second electrode to the source of electricalpulses.
 24. The method of claim 23 further comprising the step of:applying a depolarizing electrical pre-pulse to the tissue through thesecond electrode wherein the tissue near the second electrode is lesssusceptible to subsequent electric stimulation.
 25. The method of claim20 further comprising the step of implanting the source of electricalpulses within the patient's body.
 26. A method of preparing neuraltissue of the brain for subsequent electrical stimulation comprising thestep of: providing a source of electrical pulses; providing a firstelectrode; providing an electrical return path: connecting the firstelectrode to the source of electrical pulses; placing the firstelectrode in tissue of a patient's brain; and applying a hyperpolarizingelectrical pre-pulse to the tissue through the first electrode whereinthe tissue is more susceptible to subsequent electric stimulation;wherein the step of providing a first electrode includes the step ofproviding a second electrode spaced from the first electrode and furthercomprising the step of connecting the second electrode to the source ofelectrical pulses; p1 applying a depolarizing electrical pre-pulse tothe tissue through the second electrode wherein the tissue near thesecond electrode is less susceptible to subsequent electric stimulation;and wherein the step of providing a first electrode and a secondelectrode spaced from the first electrode includes the step of providinga third electrode spaced from the first and second electrodes andfurther comprising the step of connecting the third electrode to thesource of electrical pulses.
 27. The method of claim 26 furthercomprising the step of: applying a depolarizing electrical pre-pulse tothe tissue through the third electrode wherein the tissue near the thirdelectrode is less susceptible to subsequent electric stimulation. 28.The method of claim 26 further comprising the step of: applying ahyperpolarizing electrical pre-pulse to the tissue through the thirdelectrode wherein the tissue near the third electrode is moresusceptible to subsequent electric stimulation.
 29. A method ofpreparing neural tissue of the brain for subsequent electricalstimulation comprising the steps of: providing a source of electricalpulses; providing a first electrode; providing an electrical returnpath; connecting the first electrode to the source of electrical pulses;placing the first electrode on the surface of a patient's brain;applying a hyperpolarizing electrical pre-pulse to the tissue throughthe first electrode wherein the tissue is more susceptible to subsequentelectric stimulation; applying a subsequent subthreshold depolarizingelectrical pre-pulse to the tissue through the first electrode.
 30. Themethod of claim 29 wherein the step of providing an electrical returnpath includes the step of providing an electrical return path thatincludes a second electrode.
 31. The method of claim 29 wherein the stepof providing an electrical return path includes the step of providing anelectrical return path that includes the source of electrical pulses.32. The method of claim 29 wherein the step of providing a firstelectrode includes the step of providing a second electrode spaced fromthe first electrode and further comprising the step of connecting thesecond electrode to the source of electrical pulses.
 33. The method ofclaim 32 further comprising the step of: applying a depolarizingelectrical pre-pulse to the tissue through the second electrode whereinthe tissue near the second electrode is less susceptible to subsequentelectric stimulation.
 34. The method of claim 33 wherein the step ofproviding a first electrode and a second electrode spaced from the firstelectrode includes the step of providing a third electrode spaced fromthe first and second electrodes and further comprising the step ofconnecting the third electrode to the source of electrical pulses. 35.The method of claim 34 further comprising the step of: applying adepolarizing electrical pre-pulse to the tissue through the thirdelectrode wherein the tissue near the third electrode is lesssusceptible to subsequent electric stimulation.
 36. The method of claim34 further comprising the step of: applying a hyperpolarizing electricalpre-pulse to the tissue through the third electrode wherein the tissuenear the third electrode is more susceptible to subsequent electricstimulation.
 37. The method of claim 29 further comprising the step ofimplanting the source of electrical pulses within the patient's body.38. A method of preparing neural tissue of the brain for subsequentelectrical stimulation comprising the steps of: providing a source ofelectrical pulses; providing a first electrode, a second electrodespaced from the first electrode and a third electrode spaced from thefirst electrode opposite the second electrode so that the firstelectrode is generally between the second and third electrodes;providing an electrical return path; connecting the first, second andthird electrodes to the source of electrical pulses; placing the first,second and third electrodes within a patient's body in a patient'sbrain; applying a hyperpolarizing electrical pre-pulse to the tissuethrough the first electrode wherein the tissue is more susceptible tosubsequent electric stimulation; applying a depolarizing electricalpre-pulse to the tissue through the second and third electrodes whereinthe tissue near the second and third electrodes is less susceptible tosubsequent electric stimulation.
 39. The method of claim 38 furthercomprising the step of applying a subsequent depolarizing electricalpulse to the tissue through the first electrode.
 40. The method of claim39 further comprising the step of implanting the source of electricalpulses within the patient's body.
 41. A method of preparing neuraltissue of the brain for subsequent electrical stimulation comprising thesteps of: placing first, second and third electrodes in close proximityto tissue of a patient's brain; applying a hyperpolarizing electricalpre-pulse to the tissue through the first electrode wherein the tissueis more susceptible to subsequent electric stimulation; applying adepolarizing electrical pre-pulse to the tissue through a secondelectrode wherein the tissue near the second electrode is lesssusceptible to subsequent electric stimulation; and applying ahyperpolarizing electrical pre-pulse to the tissue through the thirdelectrode wherein the tissue near the third electrode is moresusceptible to subsequent electric stimulation.
 42. The method of claim41 wherein the step of placing first, second and third electrodes inclose proximity to tissue of a patient's brain includes placing thefirst electrode in tissue of a patient's brain.
 43. The method of claim42 wherein the step of placing first, second and third electrodes inclose proximity to tissue of a patient's brain includes placing thesecond electrode in tissue of a patient's brain.
 44. The method of claim43 wherein the step of placing first, second and third electrodes inclose proximity to tissue of a patient's brain includes placing thethird electrode in tissue of a patient's brain.
 45. The method of claim44 further comprising the steps of: implanting a source of electricalpulses within the patient's body; and electrically connecting the sourceof electrical pulses to the first, second and third electrodes.
 46. Themethod of claim 43 further comprising the steps of: implanting a sourceof electrical pulses within the patient's body; and electricallyconnecting the source of electrical pulses to the first, second andthird electrodes.
 47. The method of claim 42 further comprising thesteps of: implanting a source of electrical pulses within the patient'sbody; and electrically connecting the source of electrical pulses to thefirst, second and third electrodes.
 48. The method of claim 41 whereinthe step of placing first, second and third electrodes in closeproximity to tissue of patient's brain includes placing the firstelectrode on the surface of a patient's brain.
 49. The method of claim48 wherein the step of placing first, second and third electrodes inclose proximity to tissue of a patient's brain includes placing thesecond electrode on the surface of a patient's brain.
 50. The method ofclaim 49 wherein the step of placing first, second and third electrodesin close proximity to tissue of a patient's brain includes placing thethird electrode on the surface of a patient's brain.
 51. The method ofclaim 50 further comprising the steps of: implanting a source ofelectrical pulses within the patient's body; and electrically connectingthe source of electrical pulses to the first, second and thirdelectrodes.
 52. The method of claim 49 further comprising the steps of:implanting a source of electrical pulses within the patient's body; andelectrically connecting the source of electrical pulses to the first,second and third electrodes.
 53. The method of claim 48 furthercomprising the steps of: implanting a source of electrical pulses withinthe patient's body; and electrically connecting the source of electricalpulses to the first, second and third electrodes.
 54. The method ofclaim 41 wherein the step of placing first, second and third electrodesin close proximity to tissue of a patient's brain includes placing thefirst electrode near the surface of a patient's brain.
 55. The method ofclaim 54 wherein the step of placing first, second and third electrodesin close proximity to tissue of a patient's brain includes placing thesecond electrode near the surface of a patient's brain.
 56. The methodof claim 55 wherein the step of placing first, second and thirdelectrodes in close proximity to tissue of a patient's brain includesplacing the third electrode near the surface of a patient's brain. 57.The method of claim 56 further comprising the steps of: implanting asource of electrical pulses within the patient's body; and electricallyconnecting the source of electrical pulses to the first, second andthird electrodes.
 58. The method of claim 55 further comprising thesteps of: implanting a source of electrical pulses within the patient'sbody; and electrically connecting the source of electrical pulses to thefirst, second and third electrodes.
 59. The method of claim 54 furthercomprising the steps of: implanting a source of electrical pulses withinthe patient's body; and electrically connecting the source of electricalpulses to the first, second and third electrodes.